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ABSTRACT: Background: It is well-known that substandard serum valproic acid (VPA) concentrations may lead to treatment failure of epilepsy. However, there is still a lack of a quick method to predict whether a patient's serum VPA concentration will reach the standard. Objective: The aims of this study were to investigate the factors leading to substandard serum VPA concentrations in Chinese patients with epilepsy and develop a related nomogram for risk prediction. Methods: From January 2019 to March 2022, a total of 1143 serum VPA concentrations were collected from 630 hospitalized Chinese patients with epilepsy who were monitored by the Department of Pharmacy of Lu'an People's Hospital, and complete clinical data were collected from the corresponding patients for retrospective analysis. All monitored serum VPA concentrations were further divided into a training cohort and a validation cohort. For the training cohort, serum VPA concentrations below 50 µg/mL and between 50 and 100 µg/mL were classified into the subtherapeutic group and therapeutic group, respectively. The variables were selected from the clinical data, and differences between the variables of the subtherapeutic and therapeutic groups were analyzed. The influencing factors leading to substandard serum VPA concentrations were screened via logistic regression analysis, and the screened influencing factors were used to establish the nomogram prediction model. Results: Multivariate logistic regression analysis revealed that the daily dose per unit of body weight (mg/kg/d), route of administration, presence of hepatic lesions, hypoalbuminemia, and combination with carbapenems or barbiturates were independent factors influencing the occurrence of substandard serum VPA concentrations. On the basis of the results of the multivariate logistic regression analysis, a nomogram risk prediction model for substandard serum VPA concentration was established. The values of the C-index and internal verification results indicated that the nomogram model had good accuracy and discrimination. The decision curve revealed that the nomogram that predicted the risk of substandard serum VPA concentration had a greater net benefit value (ranging from 12% to 94%), indicating that the model had a wide prediction interval. Conclusions: Our study established a nomogram risk prediction model for substandard serum VPA concentrations in Chinese patients with epilepsy, which can help doctors or patients control the serum VPA concentration within the target concentration range as soon as possible.

Objective: To identify the risk factors contributing to cerebral microbleeds (CMBs), analyze the correlation between the quantity and distribution of CMBs and overall cognitive performance, including specific cognitive domains in patients, and investigate the underlying mechanisms by which CMBs impact cognitive function. Methods: Patients diagnosed with cerebral small vessel disease were recruited between September 2022 and September 2023. Clinical baseline data were systematically gathered. The Montreal Cognitive Assessment (MoCA) was employed to evaluate patients’ cognitive status. CMBs were identified via susceptibility-weighted imaging (SWI), noting their locations and quantities. Patients were categorized into two cohorts: those without CMBs and those with CMBs. This division facilitated the comparison of basic clinical data and laboratory indicators, aiming to elucidate the risk factors associated with CMBs. Within the CMBs cohort, patients were further classified based on the number of CMBs into mild, moderate, and severe groups, and according to CMBs’ locations into deep, cortical-subcortical, and mixed groups. Spearman correlation analysis and ANOVA were utilized to compare the total MoCA scores, as well as scores in specific cognitive domains, across these groups. This approach enabled the analysis of the relationship between the quantity and location of CMBs and cognitive impairment. Results: Statistically significant differences were noted between patients with and without cerebral microbleeds (CMBs) regarding gender, age, hypertension, diabetes, history of cerebral infarction, history of alcohol consumption, glycosylated hemoglobin levels, low-density lipoprotein cholesterol, and homocysteine levels ( p

Objectives Small nucleolar RNAs (snoRNAs) form clusters within the genome, representing a mysterious category of small non-coding RNAs. Research has demonstrated that aberrant snoRNAs can contribute to the development of various types of cancers. Recent studies have identified snoRNAs as potentially valuable biomarkers for the diagnosis or/and prognosis of cancers. However, there has been a lack of comprehensive reviews on prognostic and diagnostic snoRNAs across different types of cancers. Methods We conducted a systematic search of various databases including Google Scholar, Medline, Cochrane, Scopus, PubMed, Embase, ScienceDirect, Ovid-Medline, Chinese National Knowledge Infrastructure, WanFang, and SinoMed with a time frame reception to December 30, 2022. A total of 49 relevant articles were included in our analysis, consisting of 21 articles focusing on diagnostic aspects and 41 articles focusing on prognostic aspects. Pooled odds ratio, 95% confidence intervals (CIs), and hazard ratio (HR) were utilized to evaluate clinical parameters and overall survival (OS), respectively. Result The findings indicated that area under the curve, sensitivity, and specificity were 0.85, 75%, and 80% in cancer, respectively. There was a possibility that snoRNAs had a positive impact on the diagnosis (risk ratio, RR = 2.95, 95% CI: 2.75-3.16, P = 0.000) and OS (HR = 1) in cancer. Additionally, abnormally expressed snoRNAs were associated with a positive impact on OS time for chronic lymphocytic leukemia (HR: 0.88, 95%Cl: 0.69-1.11, P

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematologic disorder commonly treated with complement inhibitors such as eculizumab, ravulizumab, and pegcetacoplan. This study aims to describe treatment patterns, healthcare resource utilization, and cost for newly diagnosed PNH patients in 2 large, health insurance claims databases: MarketScan and Optum. Among the 271 patients meeting the inclusion criteria in MarketScan, 57.9% were female, and the average age was 46.6 years. Among these newly diagnosed patients, 25.1% ( n = 68) of patients received a PNH-specific pharmacologic treatment, and the average time from diagnosis to treatment was 4.7 months. The medication possession ratio was 97.0%, but discontinuation was common (58.8%). The average per-patient-per-month costs were $18,978, driven by pharmacy and infusion ($11,182), outpatient ($4086), and inpatient ($3318) costs. Despite the availability of multiple treatments, 39.9% of patients had an inpatient stay, and 50.9% had an emergency department visit. Better care management and the introduction of new treatment options are needed to address delays between diagnosis and treatment, and high rates of hospitalization and emergency department use among patients with PNH.

Background To analyze the relationship between the rotational and residual setup errors and the dose deviation on nasopharyngeal carcinoma (NPC) treated by helical tomotherapy (HT). Methods From 25 July 2017 to 20 August 2019, 16 treated NPC patients were enrolled in the study. These patients were scanned with full target range megavoltage computed tomography (MVCT) every other day. Adaptive radiotherapy function application software MIM7.1.3 were used to accumulate the actual dose. The dose deviation with the initial plan dose of the patients’ target and organs at risk (OAR) were compared, and the correlation between the dose change and the setup errors (rotational setup errors and neck residual setup error) was analyzed. Results Translational setup errors increased farther away from the head. Statistically significant difference among 3 groups was achieved in the directions of left-right ( P

The aim of this single-centre 10-year retrospective observational study was to evaluate the profile of Chinese cancerous patients complicated with venous thromboembolism (VTE) based on demographic features, clinical characteristics, and medication exposure. Consecutive 1482 patients with solid tumor complicated with VTE at a tertiary center between 2012 and 2021 were retrospectively enrolled. Data were collected on demographics, comorbidities, discharge diagnoses, laboratory examination data, treatment details, and imaging description of the lesion. The overall incidence of clinical VTE was 1.35% in hospitalized patients with cancer in our center. Lung cancer was the most frequent tumor subtype for developing VTE events, accounting for 24.83% of all cases. Over half of the patients (66.60%) were observed to have an increased risk of VTE within the first 6 months of cancer diagnosis. Close to half of the patients (46.49%) had received chemotherapy within 6 months prior to the diagnosis of VTE. The frequency of massive ascites group (＞2000 mL) in gynecological patients with VTE was significantly larger than that of nonmassive ascites group (≤2000 mL) ( P

Aims We investigated the incidence and clinical features of venous thromboembolism (VTE) in inpatients with mental illnesses. Methods We retrospectively analyzed records of inpatients with mental illnesses and confirmed VTE at The First Hospital of Hebei Medical University between August 2018 and July 2022. We recorded demographic characteristics, psychosis-related conditions, and thrombus distribution. Results Among 12939 patients diagnosed with mental illness, 156 (1.21%) presented with VTE at the first visit or during the disease course. Crude VTE incidence varied significantly across mental illnesses, being highest in patients with organic mental disorders (5.20%), followed by emotional disorders (1.10%), and others ( P

Data on the impact of morbid obesity (body mass index [BMI] ≥ 40 kg/m 2 ) on the pharmacokinetics (PK), pharmacodynamics (PD) of direct oral anticoagulants (DOACs) are relatively limited, making it difficult to design optimal dosing regimens in morbidly obese patients. To review literature on PK/PD profile, efficacy, and safety of DOACs in venous thromboembolism (VTE) and nonvalvular atrial fibrillation (AF) patients with morbid obesity and make recommendations regarding optimal dosing regimens in these patient populations. A detailed literature search was conducted (from inception to June 22, 2022) for relevant articles involving PK/PD and clinical data on DOACs use in morbidly obese patients with VTE or AF, or healthy volunteers. A total of 28 studies were identified. DOAC-specific PK variations and clinical outcomes have been observed. Obesity may have a modest effect on PK/PD of dabigatran, apixaban, or rivaroxaban. Dabigatran was effective in AF patients with morbid obesity but might increase the risk of gastrointestinal bleeding. Standard dosing of apixaban or rivaroxaban is effective and safe for VTE and AF patients with morbid obesity. Trough edoxaban concentration and anti-Xa activity were similar in different BMI groups (18.5 to >40 kg/m 2 ), and standard dosing of edoxaban may be effective and safe for AF patients. Current evidence suggests dabigatran should be used with caution in patients with AF as it might increase the risk of gastrointestinal bleeding; Standard dosing of apixaban or rivaroxaban can be used in VTE or AF patients; Standard dosing of edoxaban may be considered in AF patients.

Background: Preclinical studies often provide the evidence base for clinical studies. However, the design and reporting of preclinical trial results are inadequate, resulting in poor reproducibility and clinical translatability. We aimed to systematically evaluate the methodology and reporting quality of animal studies of acupuncture for cancer pain. Methods: About 7 databases were searched for animal research articles on acupuncture for cancer pain from the beginning of the database to January 31, 2022. ARRIVE guidelines, STRICTA, and SYRCLE risk of bias tools were used to assess the reporting quality and risk of bias of the selected studies. Results: A total of 18 studies were evaluated. Of the 22 items on the SYRCLE tool, only 6 items had a positive reporting rate of more than 50%. Of the 39 items in the ARRIVE guidelines, 14 were rated excellent, and the least frequently reported checklist items were 7. Out of the 17 STRICTA checklist items analyzed, 10 were considered appropriately reported in more than 80% of the studies, while 4 were correctly reported in less than 20%. Conclusions: Some crucial points in the design, implementation, and reporting of the experiments included in the study were not well developed, which could significantly affect the clarity, reproducibility, and translatability of the experiments. There is a need to fully implement scientific tool guidelines for future experimental studies in order to improve the quality of preclinical studies and facilitate effective translation of their results to the clinic.

Objective: The present study aimed to determine the efficacy and safety of a newly designed microwave ablation (MWA) system in ex vivo and in vivo liver model.Methods: A new MWA system (HRMW-01, Hengrui Medical, Guangzhou, China) was tested on porcine liver ex vivo with different parameter settings (50-70 W for 5-20 min). Ablation volums were measured on the gross specimens. In an in vivo study, MWA was performed at 60 W for 5 min in canine liver. Ablation volumes were identified and measured using contrast-enhanced ultrasound (CEUS) 1 w after the ablation. All animals underwent routine hematological, biochemical, and coagulation tests before ablation at 1 d and 1 w after ablation. For comparison, radiofrequency ablation (RFA) was performed using a Cool-tip system (Valleylab, Boulder, CO, USA) with an automated power setting for 12 min in both ex vivo and in vivo studies. Results: In ex vivo studies, the mean volumes of MWA coagulation ranged from 27.8 ± 7.3 cm3 to 144.6 ± 35.9 cm 3 and increased with ablation duration and power output. MWA was prone to creating larger volume but less spherical ablation shape than RFA (P < 0.05). In in vivo studies, MWA created larger ablation volumes with shorter ablation time compared to RFA (P < 0.05). Laboratory data showed significantly higher alanine aminotransferase and aspartate aminotransferase levels 1 d after ablation than based line levels (P < 0.05) while the levels decreased close to pre-ablation levels 1 w after ablation (P > 0.05). Conclusion: The newly designed MWA system is safe and more efficient than a commonly used RFA system. However, further clinical studies are warranted.

Objective To evaluate the therapeutic effect of Traditional Chinese Medicine (TCM), specifically Fuzheng Qingdu (FZQD) therapy, on the survival time of metastatic GC patients. Patients and Methods Databases of medical records of 6 hospitals showed that 432 patients with stage IV GC were enrolled from March 1, 2012 to October 31, 2020. Propensity score matching (PSM) was used to reduce the bias caused by confounding factors in the comparison between the TCM and the non-TCM users. We used a Cox multivariate regression model to compare the hazard ratio (HR) value for mortality risk, and Kaplan-Meier survival curve for the survival time of GC patients Results The same number of subjects from the non-TCM group were matched with 122 TCM-treated patients after PSM to evaluate their overall survival (OS) and progression-free survival (PFS). Median time of OS of TCM and non-TCM users were 16.53 and 9.10 months, respectively. TCM and non-TCM groups demonstrated a 1-year survival rate of 68.5% and 34.5%, 2-year survival rate of 28.6% and 3.5%, and 3-year survival rate of 17.8% and 0.0%, respectively. A statistical difference exists in OS between the 2 groups (χ 2 = 33.39 and P

Objective: This study was undertaken to investigate eukaryotic translation initiation factor 3 subunit B (EIF3B) expression and its clinical value for indicating disease progression and prognosis in adult Philadelphia chromosome negative acute lymphoblastic leukemia (Ph − ALL) patients. Methods: Totally, 76 adult Ph − ALL patients and 30 healthy donors (HDs) were included. Bone marrow (BM) samples before therapy (baseline), after 4-week therapy of Ph − ALL patients and the BM samples of HDs were collected. Then, EIF3B expression in BM was detected by reverse transcription quantitative polymerase chain reaction. Results: EIF3B expression was increased in Ph − ALL patients compared with HDs, which distinguished Ph − ALL patients from HDs (area under the curve [AUC]: 0.928; 95% confidence interval [CI]: 0.882−0.974) by receiver operating characteristic curve. Furthermore, higher baseline EIF3B expression was associated with elevated white blood cell and bone marrow blasts, while it was associated with lower complete remission (CR) within 4 weeks and less allogeneic hematopoietic stem cell transplant achievements in Ph − ALL patients. Additionally, higher baseline EIF3B expression was associated with decreased disease-free survival but not overall survival. However, it was associated with raised 1-year mortality and 3-year mortality in Ph − ALL patients. After 4-week therapy, EIF3B expression was reduced in total Ph − ALL patients. Notably, the reduction of EIF3B expression was more obvious in Ph − ALL patients who achieved CR within 4 weeks compared with Ph − ALL patients who did not achieve CR within 4 weeks. Conclusion: EIF3B overexpression is related to worsened clinical features, poor treatment response and survival in adult Ph − ALL patients.

Objective: To investigate the nonlinear relationship between age and the likelihood of undergoing prostate-specific antigen (PSA) testing, and the difference of factors influencing the test likelihood among subjects aged 40–54, 55–69, and ≥70 years. Methods: Data were extracted from the 2018 Behavioral Risk Factor Surveillance System, with the primary outcome defined as receipt of a PSA test within the previous 12 months. Restricted cubic splines were used to assess the relationship between age and the likelihood of undergoing PSA testing. Backward conditional logistic regression analyses were used to identify the predictors of undergoing PSA testing among subjects aged 40–54, 55–69, and ≥70 years. Results: Finally, 92,177 people were identified. The likelihood of PSA testing increased up to around 71 years old and then decreased rapidly for higher ages, showing a clear nonlinear inverted U-shaped relationship with age ( p < .001). Insurance status, shared decision-making, whether a recommendation for PSA testing had been accepted, income level, smoking status, and age were the common predictors of testing in the three age groups. However, the predictors differed somewhat among the three groups: being overweight or obese was only positively associated with increased testing among people aged 40–54 and ≥70 years, being retired only greatly impacted the test likelihood among those aged 40–54 years, and the general health status, marital status, and race affected people aged ≥55 years. Conclusion: The factors influencing PSA screening differ with age, which should be fully considered when screening different target age groups.

Summary: Background: Psychiatric morbidities have been associated with a risk of severe infections through compromised immunity, health behaviours, or both. However, data are scarce on the association between multiple types of pre-pandemic psychiatric disorders and COVID-19. We aimed to assess the association between pre-pandemic psychiatric disorders and the subsequent risk of COVID-19 using UK Biobank. Methods: For this cohort analysis, we included participants from UK Biobank who were registered in England and excluded individuals who died before Jan 31, 2020, (the start of the COVID-19 outbreak in the UK) or had withdrawn from UK Biobank. Participants diagnosed with a psychiatric disorder before Jan 31 were included in the group of individuals with pre-pandemic psychiatric disorders, whereas participants without a diagnosis before the outbreak were included in the group of individuals without pre-pandemic psychiatric disorders. We used the Public Health England dataset, UK Biobank hospital data, and death registers to collect data on COVID-19 cases. To examine the relationship between pre-pandemic psychiatric disorders and susceptibility to COVID-19, we used logistic regression models to estimate odds ratios (ORs), controlling for multiple confounders and somatic comorbidities. Key outcomes were all COVID-19, COVID-19 specifically diagnosed in inpatient care, and COVID-19-related deaths. ORs were also estimated separately for each psychiatric disorder and on the basis of the number of pre-pandemic psychiatric disorders. As a positive disease control, we repeated analyses for hospitalisation for other infections. Findings: We included 421 014 UK Biobank participants in our study and assessed their COVID-19 status between Jan 31 and July 26, 2020. 50 809 participants were diagnosed with psychiatric disorders before the outbreak, while 370 205 participants had no psychiatric disorders. The mean age at outbreak was 67·80 years (SD 8·12). We observed an elevated risk of COVID-19 among individuals with pre-pandemic psychiatric disorders compared with that of individuals without such conditions. The fully adjusted ORs were 1·44 (95% CI 1·28–1·62) for All COVID-19 cases, 1·55 (1·34–1·78) for Inpatient COVID-19 cases, and 2·03 (1·59–2·59) for COVID-19-related deaths. We observed excess risk, defined as risk that increased with the number of pre-pandemic psychiatric disorders, across all diagnostic categories of pre-pandemic psychiatric disorders. We also observed an association between psychiatric disorders and elevated risk of hospitalisation due to other infections (OR 1·74, 95% CI 1·58–1·93). Interpretation: Our findings suggest that pre-existing psychiatric disorders are associated with an increased risk of COVID-19. These findings underscore the need for surveillance of and care for populations with pre-existing psychiatric disorders during the COVID-19 pandemic. Funding: National Natural Science Foundation of China.

Background: Magnetic resonance (MR) black-blood thrombus imaging (BTI) is an accurate diagnostic technique for detecting deep vein thrombosis (DVT) but to date there have been no studies comparing the diagnostic performance and consistency of this technique at different field strengths. In this study, we evaluated and compared the diagnostic performance of BTI for detecting DVT at 1.5 T and 3.0 T field strengths. Methods: A total of 40 patients with DVT were enrolled in this study from November 2015 up to October 2018. All patients underwent BTI, a contrast-free T1-weighted MR imaging technique for detecting DVT, and contrast-enhanced MR venography (CE-MRV) at 1.5 T or 3.0 T field strengths. The MR data analyses used 1160 segments from the venous lumen of the 40 patients. The signal-to-noise ratio and contrast-to-noise ratio between thrombus and muscle/lumen were calculated to compare BTI at 1.5 T or 3.0 T to determine the image performance for thrombus detection at 1.5 T or 3.0 T. Two physicians blinded to the study evaluated all BTI images and calculated the overall sensitivity (SE), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV), accuracy, and diagnostic consistency at 1.5 T and 3.0 T. These images and values were compared to control CE-MRV images that had been obtained by 2 senior physicians and used as reference standards. In addition, the reliability and consistency of diagnoses between observers were also evaluated. Results: Two study-blind physicians reviewed all BTI images to diagnose thrombus and to determine SE, SP, PPV, NPV, and accuracy. There were no statistical differences in SE, SP, PPV, NPV, or accuracy between the 1.5 T and 3.0 T groups. Conclusions: Black-blood thrombus imaging has high SE, SP, and accuracy for DVT diagnosis both at 1.5 T and 3.0 T field strengths. This noninvasive diagnostic technique, which does not require the use of contrast agents, can be widely used in the clinical screening of DVT and follow-up after treatment.

Radiotherapy is one of the most important cancer treatments, but its response varies greatly among individual patients. Therefore, the prediction of radiosensitivity, identification of potential signature genes, and inference of their regulatory networks are important for clinical and oncological reasons. Here, we proposed a novel multiple genomic fused partial least squares deep regression method to simultaneously analyze multi-genomic data. Using 60 National Cancer Institute cell lines as examples, we aimed to identify signature genes by optimizing the radiosensitivity prediction model and uncovering regulatory relationships. A total of 113 signature genes were selected from more than 20,000 genes. The root mean square error of the model was only 0.0025, which was much lower than previously published results, suggesting that our method can predict radiosensitivity with the highest accuracy. Additionally, our regulatory network analysis identified 24 highly important ‘hub’ genes. The data analysis workflow we propose provides a unified and computational framework to harness the full potential of large-scale integrated cancer genomic data for integrative signature discovery. Furthermore, the regression model, signature genes, and their regulatory network should provide a reliable quantitative reference for optimizing personalized treatment options, and may aid our understanding of cancer progress mechanisms.

Most of the present anticancer drugs are highly cytotoxic and focus mainly on killing tumor cells rather than slowing the progress of cancer metastasis. Evidence has been reported that bridges the mechanisms of inflammation and tumor invasion. Therefore, we evaluated the potency in cancer metastasis chemoprevention of compounds and a coumarin extracted from Murraya exotica , which is known for its anti-inflammation bioactivity. By carrying out experiments in vitro, we found the root extracts more efficient than the leaf extracts in restraining cell migration of MDA-MB-231 cells, while leaf extracts presented slightly stronger inhibition of tumor cell adhesion at low concentrations. In addition, compared to root extracts, a novel coumarin identified previously from root extracts showed equal inhibition on cancer cell adhesion and less inhibition on cell migration. All extracts used in this study presented low cytotoxicity in vitro. Through comparison of the contents of leaf and root extracts from M exotica , several compounds are considered promising against cancer metastasis. This study evaluates the worth of further development of M exotica to find its effect on cancer metastasis chemoprevention.

IntroductionAs a result of rapid economic development in China, the lifestyles and dietary habits of its people have been changing, and the rates of obesity, diabetes, and other chronic conditions have increased substantially. We report the prevalence of type 2 diabetes and impaired fasting glucose (IFG) and the association between diabetes and overweight and obesity in Chinese adults. We also compare the results with those from the US National Health and Nutrition Examination Survey, 1999-2002.MethodsData were from adults aged 20 years or older who participated in the China National Nutrition and Health Survey, 2002 (n = 47,729). Diabetes and IFG were defined by the American Diabetes Association 2009 criteria. We assessed the prevalence of diabetes, IFG, and overweight and obesity by sex, age, region of residence, and ethnicity. ResultsThe prevalence of diabetes and IFG in Chinese adults was 2.7% and 4.9%, respectively. The prevalence of diabetes increased with age and body mass index. Men and women had a similar prevalence of diabetes, but men had a significantly higher prevalence of IFG. The prevalence of diabetes among Chinese who lived in urban areas was 2 to 3 times higher than the prevalence among those who lived in rural areas (3.9% for urban areas and 6.1% for large cities vs 1.9% for rural areas), and the prevalence of IFG was 1.5 to 2 times higher (6.1% and 8.1% vs 4.2%, respectively). The prevalence of diabetes among Chinese women and young (20-39 y) and middle-aged (40-59 y) adults who lived in large cities was similar to the prevalence of diabetes in the US population.ConclusionThe prevalence of diabetes and IFG was much higher in urban than rural areas, particularly in the large cities of China. Prevention must be emphasized among adults to reduce the future social and economic burden of diabetes in China.

Super-enhancers (SEs) are expansive cis-regulatory elements known for amplifying oncogene expression across various cancers. However, their role in cervical cancer (CC), a remarkable global malignancy affecting women, remains underexplored. Here we applied integrated epigenomic and transcriptomic profiling to delineate the distinct SE landscape in CC by analyzing paired tumor and normal tissues. Our study identifies a tumor-specific SE at the EFNA1 locus that drives EFNA1 expression in CC. Mechanically, the EFNA1 SE region contains consensus sequences for the transcription factor FOSL2, whose knockdown markedly suppressed luciferase activity and diminished H3K27ac enrichment within the SE region. Functional analyses further underlined EFNA1's oncogenic role in CC, linking its overexpression to poor patient outcomes. EFNA1 knockdown strikingly reduced CC cell proliferation, migration, and tumor growth. Moreover, EFNA1 cis-interacted with its receptor EphA2, leading to decreased EphA2 tyrosine phosphorylation and subsequent activation of the Src/AKT/STAT3 forward signaling pathway. Inhibition of this pathway with specific inhibitors substantially attenuated the tumorigenic capacity of EFNA1-overexpressing CC cells in both in vitro and in vivo models. Collectively, our study unveils the critical role of SEs in promoting tumor progression through the FOSL2-EFNA1-EphA2-Src/AKT/STAT3 axis, providing new prognostic and therapeutic avenues for CC patients.

Background: Individuals with diabetes have a significantly higher risk of developing various forms of cancer, and the potential biological links between these two diseases are not completely understood., Methods: This was a longitudinal retrospective nationwide cohort study, a study design that allows us to examine the natural course of cancer development over an extended period of time with a large sample size. Initially, 3,111,975 and 22,208,395 eligible patients aged ≥ 20 years with and without diabetes, respectively, were matched by age, sex, and the Charlson comorbidity index. Ultimately, 1,751,457 patients were selected from each group. Stratified populations for diabetic retinopathy (DR) (n = 380,822) and without DR (n = 380,822) as well as proliferative DR (PDR) (n = 141,150) and non-proliferative DR (NPDR) (n = 141,150) were analyzed in this study. The main outcome measure was the first-time diagnosis of cancer during the follow-up period., Results: We observed a 20% higher risk of total cancer incidence [hazard ratios (HR), 1.20; p < 0.001] in the diabetes cohort compared to the non-diabetes cohort. The highest HR was observed for liver and pancreas cancers. Moderately increased risks were observed for oral, colon, gallbladder, reproductive (female), kidney, and brain cancer. Furthermore, there was a borderline significantly increased risk of stomach, skin, soft tissue, female breast, and urinary tract (except kidney) cancers and lymphatic and hematopoietic malignancies. The stratified analysis revealed that the total cancer incidence was significantly higher in the DR cohort compared to the non-DR cohort (HR, 1.31; p < 0.001), and there was a borderline increased risk in the PDR cohort compared to the NPDR cohort (HR, 1.13; p = 0.001)., Conclusions: This study provides large-scale, nationwide, population-based evidence that diabetes is independently associated with an increased risk of subsequent development of total cancer and cancer at specific sites. Notably, this risk may further increase when DR develops., (© 2024. The Author(s).)

Background: Early Identifying and characterizing patients with diabetic macular edema (DME) is essential for individualized treatment and outcome optimization. This study aimed to timely investigate optical coherence tomography (OCT) biomarkers of DME refractory to intravitreal anti-vascular endothelial growth factor (VEGF) therapy., Methods: We retrospective reviewed 72 eyes from 44 treatment-naïve patients who were treated with intravitreal anti-VEGF for DME. OCT scans prior to anti-VEGF were evaluated for serous retinal detachment (SRD), size of outer nuclear layer cystoid changes, diffuse retinal thickening, integrity of the inner segment-outer segment (IS-OS) junction, quantity and location of hyperreflective foci, vitreomacular interface abnormalities, and epiretinal membrane (ERM). The Baseline best-corrected visual acuity (BCVA) and central macular thickness was recorded at baseline and 4 months after treatment with anti-VEGF. The main outcome measure was the correlation between spectral-domain OCT measurements and BCVA response at baseline and after anti-VEGF treatment (mean change from baseline; ≥ 10 Early Treatment Diabetic Retinopathy Study letters in BCVA)., Results: Partially continuous IS-OS layers (partially vs. completely continuous: β, -0.138; Wald chi-square, 16.392; P<0.001) was predictor of better response to anti-VEGF treatment. In contrast, ERM (present vs. absent ERM: β, 0.215; Wald chi-square, 5.921; P=0.015) and vitreomacular traction (vitreomacular traction vs. posterior vitreous detachment: β=0.259; Wald chi-square=5.938; P=0.015) were the predictors of poor response. The improvement of BCVA trended toward the OCT predictive value of central macular thickness reduction; however, this was not significant., Conclusion: Partially continuous IS-OS layers is predictive of better response to anti-VEGF therapy in DME. Meanwhile, ERM is a significant predictor of poor response., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hsieh, Deng, Chang, Chang and He.)

Purpose: Work-related ocular trauma remains the leading cause of unilateral visual impairment worldwide. Many preventable work-related ocular injuries continue to occur, even at home. This study describes the characteristics, surgical techniques, and prognostic factors of lawn trimmer-related open-globe injuries in eastern Taiwan., Methods: This was a retrospective, consecutive case series study. Slit-lamp biomicroscopy, dilated fundoscopy, and orbital computed tomography (CT) images were collected., Results: Twenty-six eyes of 26 patients were enrolled in the study. Fifteen patients (57.7%) had an intraocular foreign body (IOFB). The IOFB was metallic in 13 cases and glass and stone in the other 2 cases. Seven IOFBs (46.7%) were retained in the anterior chamber, 7 (46.7%) in the posterior segment, and 1 (6.7%) in the intraconal space. Univariate analysis showed that the presence of IOFB trended toward the development of endophthalmitis; however, this was not statistically significant (hazard ratio, 2.25; 95% confidence interval 0.35-14.61; P = 0.658). Eleven patients had metallic IOFBs noted on CT scans with metal artifacts, whereas two patients had small metallic IOFBs without metal artifacts. One patient had a glass IOFB mimicking metal artifacts on the CT scan. In one case, CT failed to reveal the IOFB, and an intralenticular metallic foreign body was incidentally found intraoperatively., Conclusion: Our study provides a broad characterization of lawn trimmer-related open-globe injuries. The informative and diverse findings of IOFBs on CT scans will help clinicians detect and recognize IOFBs more precisely and perform the surgery without causing further damage., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Background/purpose: Shwachman-Bodian-Diamond syndrome (SBDS) protein is widely present in eukaryotes from vertebrates to protozoa. However, there are several variants within species, and previous studies have shown evidence that they may have additional functions. There are two SBDS-related proteins in Acanthamoeba. One is an rRNA metabolism protein of the SBDS family (ACA1&#95;142090), and the other is SBDS (ACA1&#95;204560). Although there is a conserved SBDS domain in the Acanthamoeba SBDS (ACA1&#95;204560; AcSBDS), its function has not been reported. The aims of this study were to characterize the expression of AcSBDS during phagocytosis and encystation., Methods: AcSBDS-specific primer was designed to amplify the genomic AcSBDS of Acanthamoeba ATCC-30010. The AcSBDS expression was examined using reverse transcription polymerase chain reaction (RT-PCR) and immunostaining after phagocytosis and encystation treatment., Results: In this study, we found that the mRNA expression level of AcSBDS increased rapidly and that alternative splice variants were detected during phagocytosis and encystation processes. The results of immunofluorescence staining showed that the AcSBDS proteins accumulated surrounding phagocytosed bacteria., Conclusion: Our results suggest that AcSBDS may not only have ribosomal maturation features but also have cytoskeleton-associated functions related to phagocytosis and encystation., Competing Interests: Declaration of Competing Interest All authors declare no conflicts of interest., (Copyright © 2019. Published by Elsevier B.V.)

Purpose: To examine the risk of open-angle glaucoma (OAG) among patients receiving alpha1-adrenoceptor (α1-AR) antagonists for lower urinary tract symptoms (LUTS)., Methods: This was a nationwide, population-based, retrospective cohort study from Asia/Taiwan. One million beneficiaries were randomly sampled from among 27.38 million individuals enrolled in the National Health Insurance program, and subjects with a diagnosis of LUTS from 2001 to 2012 were identified (N = 105,341). After 1:1 propensity score matching by gender, age, comorbid medical diseases, number of all medical visits during the observational period, and index date, 4081 patients were enrolled in the study group, comprised of patients who had taken α1-AR antagonists, and 4081 patients were enrolled in the control group, comprised of patients who had never taken α1-AR antagonists. The incidence and risk of OAG (defined as two ambulatory visits with a ICD-9 diagnosis code 365, excluding ICD-9 diagnosis codes 365.2-365.6, 365.02, 365.03, 365.13, 365.14, and 365.8) were calculated., Results: Patients taking α1-AR antagonists had a higher incidence ratio of 1.86 (95% confidence interval [CI], 1.30-2.65) for developing OAG. After adjusting for age, gender, and comorbidities, the hazard ratio (HR) for OAG for patients taking α1-AR antagonists was 1.66 (95% CI, 1.16-2.39; P = 0.006). Among patients with hypertension, the hazard ratio for OAG associated with taking α1-AR antagonists increased to 1.79 (95% CI, 1.07-2.99; P = 0.003). On the other hand, the association of α1-AR antagonists with OAG was not significant among patients with diabetes mellitus, hyperlipidemia, or older age., Conclusions: The findings of our study suggest an increased risk for OAG among patients taking α1-AR antagonists for LUTS, especially in patients with hypertension.

β-Lactams are well known as the best antibiotics for inhibiting the cross-linking between adjacent polysaccharide chains and peptides in the peptidoglycan layer of bacterial cell walls, causing bacterial cell lysis. There are no reports on the action of and resistance mechanisms to β-lactams in protozoa. Acanthamoeba castellanii is a free-living protozoan pathogen capable of causing blinding keratitis and fatal granulomatous encephalitis. When Acanthamoeba is exposed to harsh conditions, it differentiates into the cyst stage to avoid environmental stresses, such as drug treatment. In this study, it was shown that the mature encystation rate of A. castellanii is decreased by treatment with cefotaxime (CTX) and clavulanic acid (CLA); however, the drugs do not kill the amoeba. We hypothesise that β-lactam antibiotics may disturb synthesis of the double cell wall during the encystation process of Acanthamoeba. Interestingly, CTX is considered a powerful β-lactam, whereas CLA is considered a weak β-lactam but an efficient β-lactamase inhibitor. It was demonstrated that Acanthamoeba expresses β-lactamases to prevent inhibition of the encystation process by β-lactams. To reveal the functions of Acanthamoeba β-lactamases, a recombinant Acanthamoeba β-lactamase was produced in Escherichia coli that conferred resistance to β-lactams such as CTX, cefuroxime, penicillin and meropenem. Consequently, we suggest that Acanthamoeba produces enzymes similar to β-lactamases to avoid interference from the environment. Here we provide a new point of view on an important gene responsible for drug resistance and advocate for the development of more efficient treatment against Acanthamoeba infection., (Copyright © 2019 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Using Saccharomyces cerevisiae as an experimental model, the potential toxicological effects of Fe 3 O 4 nanoparticles (Fe 3 O 4 -NPs) were investigated following exposure to 0-600 mg/L for 24 h. Results revealed that cell proliferation was significantly inhibited by Fe 3 O 4 -NPs with an IC 50 value of 326.66 mg/L. Mortality showed a concentration-dependent increase, and the highest concentration in this study (600 mg/L) resulted in 22.30% mortality. In addition, Effects on proliferation and mortality were accounted for Fe 3 O 4 -NPs rather than iron ion released from Fe 3 O 4 -NPs. Scanning and transmission electron microscope observation showed that Fe 3 O 4 -NPs extensively attached on the cell surfaces, causing cells to deform and shrink. Moreover, Fe 3 O 4 -NPs could be internalized in S. cerevisiae cells via endocytosis and then be distributed in cytoplasm and vesicles. The data of uptake kinetics demonstrated that the maximal accumulation (4.898 mg/g) was reached at 15 h. Besides, percentage of late apoptosis/necrosis was observably increased (p < 0.01) at 600 mg/L (15.80%), and the expression levels of apoptosis-related genes (SOD, Yca1 and Nuc1) were dramatically increased following exposure to Fe 3 O 4 -NPs for 24 h. As expected, mitochondrial transmembrane potential was significantly decreased (p < 0.01) at 50-600 mg/L, and biomarkers of oxidative stress (ROS, CAT and SOD) were also markedly changed following exposure. Altogether, the combined results so far indicated Fe 3 O 4 -NPs could induce S. cerevisiae cell apoptosis that mediated by mitochondrial impairment and oxidative stress., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: To describe a peculiar case of concurrent non-arteritic anterior ischemic optic neuropathy (NAION) and cilioretinal arteries occlusion (CLRAO) without other causative agents which responded well to intravenous and intravitreal injection of corticosteroids., Case Presentation: A 41-year-old woman presented with painless vision loss in the right eye for 1 week. Fundus examinations showed marked disc swelling, flame-shaped hemorrhage over the superior nerve fiber area, and well-demarcated retinal ischemia superior to the fovea in the right eye. Under the impression of NAION with branch retinal artery occlusion, the patient was treated with intravenous and intravitreal injection of corticosteroids. Two months later, as the disc swelling and retinal ischemia resolved, we found that the occluded artery was the cilioretinal artery and not the ordinary branch retinal artery., Conclusions: CLRAO may be concomitant with the setting of NAION, the physicians should be aware that CLRAO may be misinterpreted as BRAO owing to profound disc edema during the early stages of the disease.

Desert ecosystem has unique drought-enduring plants and stoichiometric characteristics. We collected leaf samples of 67 plant species from 63 desert sites in Xinjiang, and explored foliar carbon (C), nitrogen (N) and phosphorus (P) stoichiometry and the relationship between leaf nutrient stoichiometry and climatic factors. The results showed that the average content of leaf C, N and P in these plants were 394, 18.4 and 1.14 mg·g -1 , respectively. The mean values of C:N, C:P and N:P were 28, 419 and 18, respectively. In general, shrubs had higher leaf N content than trees and herbs, while leaf P content was lower (higher) in shrubs than in herbaceous plants (trees). Plants with C3 photosynthesis pathway had higher leaf C, N, C:P and N:P than those with C4 pathway. With increasing mean annual precipitation, leaf C first decreased and then increased, while both leaf N and P showed the opposite trend. Leaf C:N and C:P first decreased and then increased, while leaf N:P changed insignificantly. With increasing mean annual temperature, leaf C first decreased and then increased, and leaf N and P decreased, while leaf C:P and N:P increased. Leaf C:N did not change significantly with mean annual temperature. Mean annual precipitation generally showed stronger control on the variation of leaf nutrient stoichiometry than MAT and plant functional types. These results could help predict responses of the biogeochemical cycling of C, N and P to the global climate changes and provide reference and basic data for biogeochemical modeling in the arid regions.

The target of eliminating measles has not been achieved, and measles has resurged in Zhejiang, China, since 2013. In this study, we hypothesized that population density and the proportion of the floating population were the potential causes of measles persistence in Zhejiang. Measles cases in Zhejiang from 2004 through 2017 were analyzed using data from the National Notifiable Diseases Reporting System (NNDRS). Reported measles incidence and annual incidence by age were described. Spearman correlation coefficients were used to assess correlations between measles incidence and population density and the proportion of floating population. A total of 48,648 measles cases were reported during the 14-year period. Two large measles epidemics occurred in 2005 (14,317 cases, incidence of 29.38/100,000) and 2008 (12,782 cases, incidence of 25.26/100,000). A higher proportion of cases occurred in young adults aged 20 to 34 years and infants under 1 year of age. A positive correlation was observed between measles incidence and either population density or proportion of inter-provincial floating populations. In general, Zhejiang suffers from a high incidence of measles partly because of its high population density and the low vaccination rates among inter-provincial floating populations. To meet the target of measles elimination, convincing susceptible young adults and migrant children to get vaccinated remains a critical issue.

Objective: To investigate the relationship between diabetes and future development of age-related macular degeneration (AMD)., Research Design and Methods: Longitudinal, retrospective cohort study data for the period between 1997 and 2012 were obtained from the Longitudinal Health Insurance Database (LHID) of Taiwan. The final available 71,904 patients with diabetes and 270,213 patients without diabetes ≥50 years of age were further matched by age, sex, and Charlson comorbidity index. In the end, 54,616 study subjects in each of the diabetes and nondiabetes groups were recruited. The stratified populations of patients with diabetes with diabetic retinopathy (DR) ( n = 7,119) versus those with diabetes who do not have DR ( n = 7,119) and populations of patients with proliferative DR (PDR) ( n = 2,134) versus those with nonproliferative DR (NPDR) ( n = 2,134) were also obtained. Competing risk regression models were used to assess the adjusted hazard ratio (HR) and 99% CI. The main outcome measures were the first-ever diagnosis of AMD during the observational period., Results: The incidences of nonexudative AMD (HR 1.23; P = 0.108) and exudative AMD (HR 1.37; P = 0.023) were not significantly associated with cohorts of persons with diabetes compared with cohorts without diabetes. The stratified analysis showed that nonexudative AMD (HR 3.89; P = 0.001) and exudative AMD (HR 3.42; P < 0.001) were significantly correlated to diabetes with DR cohorts, compared with diabetes without DR cohorts. The incidences of nonexudative AMD (HR 0.53; P = 0.277) and exudative AMD (HR 2.27; P = 0.058) were not significantly different between PDR cohorts compared with NPDR cohorts., Conclusions: This study provides large-scale, population-based evidence that diabetes with retinopathy is independently associated with an increased risk of subsequent AMD development., (© 2018 by the American Diabetes Association.)

Objective: To examine the correlation between mean arterial pressure (MAP) and wound healing indices and describe an analytical process that can be used accurately and prospectively when evaluating all types of skin ulcerations., Methods: A correlational study in a long-term-care facility.Participants (N = 230) were adults residing in a long-term-care facility with an average age of 77.8 years (range, 35-105)., Main Outcome Measures: Assessment through both an index of wound healing and wound surface area. Signs of wound healing included a reduction of surface area and surface necrosis and increased granulation or epithelialization., Results: Aggregate analyses for all wound locations revealed a positive correlation between the MAP and index of wound healing (r = 0.86, n = 501, P < .0001). A well-defined positive correlation between the MAP and stalled or poor wound healing was noted for all wound locations in this data set when MAP values were 80 mm Hg or less (r = 0.95, n = 141, P < .0001). Further, the data set of truncal wounds and MAP of less than 80 mm Hg yielded a very strong positive correlation. The data indicated that as perfusion decreased, wounds within the sample population declined (r = 0.93, n = 102, P < .0001)., Conclusion: The data suggest that MAP values less than 80 mm Hg can independently result in stalled wound healing or worsened wounds. A predictability of wounds stalling or declining related to the MAP was observed, regardless of topical treatment or standard-of-care interventions. Therefore, the data also suggest that remediating states of low perfusion should take precedence in making treatment decisions.

Objective: To evaluate the changes in retinal functions using multifocal electroretinography (mfERG) following intravitreal injection of Lucentis for treatment of wet age-related macular degeneration., Methods: This prospective study was conducted in 14 patients (9 men and 5 women, 14 eyes) with wet age-related macular degeneration receiving treatment with intravitreal injections of ranibizumab (Lucentis) in our hospital between October, 2014 and January, 2016. All the patients received the treatment following a 1+PRN protocol and after the initial injection, the patients were followed up monthly for 6 months to decide if additional injections were needed. The corrected visual acuity and mfERG findings of the patients were assessed before and at l, 3 and 6 months after the initial injection., Results: At the last follow-up, the patients received injections for a mean of 2.86∓1.58 times. The best corrected visual acuity (BCVA) at 1 month after the initial treatment was not significantly different from that before treatment (P=0.07), but showed significant improvements at 3 and 6 months (P<0.05). In mfERG, the implicit time of the 6 rings showed no significant decrease after the treatment, but the amplitude density of P1 and N1 in rings 1 and 2 improved significantly at 1, 3, and 6 months after the initial injection (P<0.05)., Conclusion: Multifocal electroretinography can serve as a useful modality for evaluating visual function changes in patients receiving intravitreal injection of Lucentis for wet age-related macular degeneration.

BACKGROUND Wear particle-induced peri-implant loosening is the most common complication affecting long-term outcomes in patients who undergo total joint arthroplasty. Wear particles and by-products from joint replacements may cause chronic local inflammation and foreign body reactions, which can in turn lead to osteolysis. Thus, inhibiting the formation and activity of osteoclasts may improve the functionality and long-term success of total joint arthroplasty. The aim of this study was to interfere with CXC chemokine receptor type 2 (CXCR2) to explore its role in wear particle-induced osteolysis. MATERIAL AND METHODS Morphological and biochemical assays were used to assess osteoclastogenesis in vivo and in vitro. CXCR2 was upregulated in osteoclast formation. RESULTS Local injection with adenovirus-mediated siRNA targeting CXCR2 inhibited titanium-induced osteolysis in a mouse calvarial model in vivo. Furthermore, siCXCR2 suppressed osteoclast formation both directly by acting on osteoclasts themselves and indirectly by altering RANKL and OPG expression in osteoblasts in vitro. CONCLUSIONS CXCR2 plays a critical role in particle-induced osteolysis, and siCXCR2 may be a novel treatment for aseptic loosening.

Varicella zoster virus-associated neuroretinitis is rare. We report a patient who presented with blurred vision of the left eye and extraocular movement pain. A fundoscopic examination revealed disc edema, hyperemia, and macular edema. The impression was neuroretinitis. Intravenous methylprednisolone pulse therapy was administered. However, visual recovery was incomplete with optical coherence tomography (OCT) imaging showing photoreceptor layer disruption. The laboratory data were rechecked and demonstrated a high varicella zoster virus immunoglobulin G titer. Varicella zoster virus-associated neuroretinitis was suspected and oral acyclovir was prescribed. His visual acuity improved to 0.9 after 2 weeks of treatment, and OCT showed photoreceptor layer restoration. Spectrum-domain OCT provides useful information when evaluating the disease course of neuroretinitis., Competing Interests: Conflicts of interest: None of the authors has any conflicts of interest to declare.

Proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR) are characterized by the development of epi-retinal membranes which may exert a tractional force on retina. A lot of inflammatory growth factors may disturb the local ocular cells such as retinal pigment epithelial (RPE) cells, causing them to migrate and proliferate in the vitreous cavity and ultimately forming the PVR membrane. In this study, the signal pathways mediating cell migration of RPE induced by growth factors were investigated. Hepatocyte growth factor (HGF), epidermal growth factor (EGF) or heparin-binding epidermal growth factor (HB-EGF) induced a greater extent of migration of RPE50 and ARPE19 cells, compared with other growth factors. According to inhibitor studies, migration of RPE cells induced by each growth factor was mediated by protein kinase C (PKC) and ERK (MAPK). Moreover, HGF coupled with EGF or HB-EGF had synergistic effects on cell migration and enhanced activation of PKC and ERK, which were attributed to cross activation of growth factor receptors by heterogeneous ligands. Furthermore, using the shRNA technique, PKCδ was found to be the most important PKC isozyme involved. Finally, vitreous fluids from PVR and PDR patients with high concentration of HGF may induce RPE cell migration in PKCδ- and ERK- dependent manner. In conclusion, migration of RPE cells can be synergistically induced by HGF coupled with HB-EGF or EGF, which were mediated by enhanced PKCδ activation and ERK phosphorylation.

Purpose: Our previous report demonstrated that ethambutol (EMB) might induce cytoplasmic vacuolization and reduce the uptake of photoreceptor rod outer segments (ROS) in retinal pigment epithelium (RPE) cells, which are mediated via a protein kinase C (PKC)-dependent pathway. In the present study, we sought to identify the PKC isozyme(s) involved., Methods: EMB-induced cytoplasmic vacuolization and uptake of ROS were observed under a phase contrast microscope. Western blots were performed to observe the membrane translocation of PKC isozymes and cytoplasmic release of cathepsin D. Quantitative PCR were performed to analyze gene expression of PKCδ. Human RPE cell line RPE50 and ARPE19 cells were pretreated with specific inhibitors or transfected with shRNAs of various PKC isozymes, including PKCα, β, ε, γ, and δ, to examine whether EMB-induced toxic effects were prevented., Results: In RPE50 cells, gene expression of PKCδ on both mRNA and protein levels was induced by EMB within 30 min to 3 h. EMB-induced cytoplasmic vacuolization in both RPE50 and ARPE19 cells was prevented by pretreating the cells with a specific inhibitor of PKCδ, Rottlerin, or depletion of PKCδ by shRNA. EMB-triggered reduction of ROS uptake was also significantly suppressed by pretreatment with Rottlerin, or depletion of PKCδ by shRNA technology. In contrast, pretreatment of the cells with specific inhibitors of PKCα, β, ε, or γ, or depletion of PKCα or β didn't influence the aforementioned EMB-triggered toxic effects. In addition, in RPE50, EMB induced the release of lysosomal enzyme cathepsin D into cytosol within 30 min to 6 h, which was also prevented by Rottlerin., Conclusions: EMB-induced vacuole formation, cytoplasmic release of cathepsin D, and reduction of phagocytosis in RPE are intimately correlated and regulated by the PKCδ signal pathway.

Objective: To study the difference between two internal fixation methods Kaneda and Z-plate in the operation of anterior surgical approach and decompression after thoracolumbar fractures., Methods: The bio-mechanical structure of the internal fixture, install when operating, complications and time of the operation were compared in the cases by Kaneda and Z-plate., Results: Z-plate method had the following characteristics: reasonable of the bio-mechanical structure; stability after internal fixture being installed; capability of completely propping up the injured centrum and keeping the height of middle-column; simple operation when installing internal fixture and shorter time of operation (1.1 hours, P < 0.05); fewer complications., Conclusion: Z-plate is an ideal internal fixation method in the operation of anterior surgical approach after thoracolumbar fractures.

A new species of the subgenus Larroussius Nitzulescu 1931, named Phlebotomus lengi in honour of the Chinese sandfly taxonomist Professor Yan Jia Leng, was found amongst the phlebotomine sandflies collected in Yunnan Province, China, in 1989. A full description of the male and female of this species is provided. The ascoid formula of P. lengi distinguishes it from all previously described members of the subgenus Larroussius.